Although a small field in medicine, dermatological diseases are very frequent and span a wide range of illnesses such as allergies, inflammation (e.g. atopic dermatitis, psoriasis), autoimmune diseases or malignancies (e.g. melanoma). Thus, translational dermatological research is an important, innovative field for future basic and clinical research for many diseases in which treatment is still an unmet medical need.
Skin conditions under investigation
The major areas of dermatology under investigation at the Charles Institute are atopic dermatitis, rosacea, itch and other inflammatory skin conditions (Director: Professor Martin Steinhoff, Professor Frank Powell), cell signalling (Professor Cormac Taylor), wound healing and epidermolysis bullosa (Dr Wenxin Wang) and melanoma genetics (Dr Simon Furney). These areas are explored using a wide range of innovative techniques: disease models, 3D skin models, proteomics, genomics, metabolomics, cell signalling, immunology, systems biology, and state-of-the-art imaging.
Itch serves as a self-protective system under normal conditions, but chronic itch can have a debilitating impact on the quality of life. The chronic itch can be caused by skin conditions such as atopic dermatitis (eczema) and contact dermatitis, or after zoster (shingles), by systemic disorders or certain medications. Terminally ill cancer patients, for example, often experience such severe itch in response to morphine that many choose to live in pain rather than take the medication. Steinhoff’s laboratory is discovering more about the mechanisms of itch (Fig. 1). A large part of their work focuses on endothelin-1, and they have shown that it is possible to turn the dial up or down on the level of itch by targeting this pathway.
Epidermolysis bullosa is a family of genetic skin diseases characterised by skin fragility, resulting in blisters, chronic wounds, scarring and skin cancer. In an effort to find a cure to this devastating disease, the Wang team has developed a non-viral, polymer-based vector carrying normal collagen type VII expression to cells in which it is missing. Unlike most genetic therapies, this is designed to be applied directly to the skin. Wang’s laboratory designs and builds polymers with a variety of defined shapes illustrated in Fig. 2 which can be specifically tailored to suit the application. This distinctive combination of chemical and biological expertise offers promising prospects for application to many areas of bioscience, including drug delivery, immunology and the development of vaccines, bio-detection and biosensor, antimicrobials and antiviral agents.
Another target group of patients in Wang’s sights is people with diabetes. Over time, diabetes can damage the nerves and circulation of the lower limbs, and if wounds form they can be very hard to heal and in severe cases, the person may need an amputation. The Wang group has been looking at the specific needs of diabetic wounds and has developed a tailored biomaterial that could be used in dressings to carry therapeutic agents such as stem cells and growth factors. Rosacea is a chronic inflammatory skin disorder with symptoms of dry, sensitive facial skin that commonly affects middle-aged people, with a particularly high incidence among people of Celtic extraction. As an example of modern translational research, Steinhoff’s recent findings gave new insights into the pathophysiology of rosacea, which is so far incompletely understood. Using a combination of transcriptomics and immunohistochemistry, his group elucidated for the first time the complex pathways of genes involved in this condition (Journal of Investigative Dermatology 2015). Another approach led by Prof. Frank Powell focuses on deciphering the role of the Demodex mite, a microscopic organism associated with the inflammatory lesions which affect rosacea patients.
Translational research
At the UCD Charles Institute of Dermatology, the vision is to establish a centre of excellence for translational dermatology research in Ireland, working with colleagues in dermatology clinics at UCD’s affiliated hospitals. The goal is to understand the pathophysiology of skin diseases in a translational fashion. The outstanding infrastructure with patient care clinics, clinical trial units, and a new €20m research centre for over 70 scientists provides a unique opportunity to comprehensively study the pathophysiology of various skin diseases, develop new treatments and perform innovative clinical trials for patients with treatment-resistant skin diseases.
Funding
Avon; Bayer; Bristol Myers-Squibb; Chugai; the City of Dublin Skin and Cancer Hospital Charity; DEBRA International; Galderma; German Research Foundation; Leo Foundation; L’Oreal; Maruho; National Institutes of Health (NIH); Pfizer; Salix; Science Foundation Ireland; Tigercat; Toray; Vertex.
Director biography
Professor Martin Steinhoff is a clinical dermatologist as well as a basic scientist with 20 years’ experience in translational dermatological research. He is a trained dermatologist, allergist and phlebologist with specific interests in neuroimmunology, inflammatory skin diseases and systems medicine. After his appointment as an associate professor in Germany (2005-2008), he worked at the University of California, San Francisco, as full professor (2009- 2013) with NIH-funded research. Steinhoff began his position as professorial chair of dermatology and director of the UCD Charles Institute of Dermatology in January 2014.
Prof Martin Steinhoff
Skin Disease Research – University College Dublin
Tel: +353 1 7166261
martin.steinhoff@ucd.ie
